This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Perhaps the most outstanding contribution by cryoEM is the ability to image macromolecular assemblies under nearly native conditions. However, the drawback to this is that the sample is often a mixture of macromolecules in different conformations, reflecting the natural and intrinsic behavior of a biological machine. Computational and biochemical approaches have sought to isolate these individual conformations, allowing for the processing and eventual reconstruction of several structures in the different conformations. This will provide us with a unique opportunity to visualize the structural dynamics of these machines in a series of snapshots, but stops short of answering more fundamental questions about the motions associated with the different conformations.